The present invention concerns a new therapeutic application of the inner ester derivatives of gangliosides.
U.S. Pat. No. 4,476,119 and European Pat. No. 0072722 describe the preparation of the inner ester gangliosides and the use of the compounds as being valuable agents in the treatment of pathologies affecting the nervous system after trauma or diseases which in some way damage the nervous tissue, and as being more efficacious than gangliosides themselves.
The present invention reports the significant analgesic-antiinflammatory activity of individual inner ester gangliosides, in particular the inner ester of GM.sub.1, and of a mixture of inner ester gangliosides.
Gangliosides are a group of glycosphingolipids with a structure containing one saccharide part bound to a ceramide and to a sialic group. The saccharide part is composed of at least one galactose or glucose and of at least one N-acetylglucosamine or N-acetylgalactosamine.
The general structure of a ganglioside may therefore be represented by the following formula:
______________________________________ one mole of ceramide at least one mole of galactose or glucose one mole of sialic acid at least one mole of N-acetylglucosamine or N-acetylgalactosamine ______________________________________
in which these compounds are bound by glucosidic bonds.
Numerous gangliosides have been identified which have proved to be particularly abundant in the nervous tissue, especially in that of the brain. Various studies have demonstrated that the sialic groups most frequently encountered in gangliosides are N-acetylneuraminic acid (NANA) and to a lesser extent, N-glycolylneuraminic acid. Of the numerous gangliosides identified, the following gangliosides, classified by their international symbols, were found to exist in considerable measure in the mixtures derived from bovine brain tissue: ##STR1## where Glc stands for glucose, GalNAC stands for N-acetylgalactosamine, Gal stands for galactose, NANA stands for N-acetylneuraminic acid and the percentages in parenthesis indicate the quantity of each ganglioside found in a mixture of gangliosides extracted from bovine brain tissue.
It is well known that gangliosides play an important role in the nervous system and it has recently been shown that gangliosides are useful in therapy for pathologies of the peripheral and central nervous systems [Acta Psychiat. Scand., 55, 102, (1977); Brain Res. 197, 236, (1980); Drugs of Today 22, 73-107, (1986)].
The therapeutic action of gangliosides seems to consist above all in stimulating sprouting phenomena of the nerve cell and in activating the membrane enzymes implicated in the conduction of nervous stimuli, such as for example the enzyme (Na.sup.+,K.sup.+)ATPase [Brain Res., 197, 236, (1980), J. of Neurochem. (1981)].
Neuronal sprouting stimulated by gangliosides enhances functional recovery of the damaged nervous tissue.
Subsequent studies have shown that inner ester gangliosides are more efficacious than starting gangliosides in the therapy of nervous system pathologies. See for example the above-noted U.S. Pat. No. 4,476,119.
It is also known that gangliosides have a specific and strong antinociceptive activity, that is, they are efficacious in reducing writhings induced by phenylquinone and acetic acid and the increase in permeability induced by acetic acid [Arch. Int. Pharmacodyn. 272, 103-117 (1984)].